Diagnostic Accuracy And Cost-Effectiveness Of Different Strategies To Triage Adnexal Masses: A Prospective Study

BACKGROUND: Transvaginal ultrasonography (TVS) and serum biomarkers are widely used in clinical practice to triage adnexal masses, but the effectiveness of current biomarkers is quite weak. OBJECTIVES: To determine the best way to diagnose the patients with adnexal masses, in terms of diagnostic accuracy and economic costs, among four triage strategies: International Ovarian Tumor Analysis group's simple rules (SR) for the interpretation of TVS with the addition of subjective assessment (SA) by an experienced ultrasound operator only when TVS results are inconclusive (hereafter defined as SR±SA), SR±SA+CA125, SR±SA+HE4, and SR±SA+ROMA. Our main hypothesis was that the addition of the biomarkers (CA125, HE4 or ROMA algorithm) to SR±SA could improve the triage of these patients in terms of diagnostic accuracy (i.e., malignant versus benign). As secondary analyses we estimated the cost-effectiveness of the four strategies and the diagnostic accuracy of SR±SA at the study hospitals. METHODS: From February 2013 to January 2015, 447 consecutive patients who were scheduled for surgery for an adnexal mass at the S.Anna and Mauriziano Hospitals in Turin were enrolled in this multi-center prospective cohort study. Preoperative TVS was performed and preoperative CA125 and HE4 levels were measured. Pathology reports were used to assess the diagnostic accuracy of the four triage strategies, and the costs of each strategy were also calculated. RESULTS: 391 patients were included in the analysis: 57% (221) were premenopausal and 43% (170) were postmenopausal. The overall prevalence of malignancy was 21%. SR were conclusive in 89% of patients; the overall performance of SR±SA was: sensitivity 82%, specificity 92%, and positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio: 74%, 95%, 10.5, and 0.19, respectively. In premenopausal women, mean costs varied from €36.4 for SR±SA, to €70.1 for SR±SA+ROMA. The addition of biomarkers to SR±SA showed no diagnostic advantage compared to SR±SA and was also more costly. Among postmenopausal women, mean costs varied from €39.5 for SR±SA, to €73.2 for SR±SA+ROMA. SR±SA+CA125 and SR±SA+ROMA had a higher sensitivity (92%, 95% confidence interval [CI] 85-99% for both) than SR±SA (81%, 95% CI 71-91%), but SR±SA had a higher specificity (84%, 95% CI 77-91%). SR±SA+CA125 and SR±SA+ROMA improved diagnostic accuracy, each diagnosing 33.3% more malignant adnexal masses. Compared to SR±SA alone, SR±SA+CA125 showed a net reclassification improvement (NRI) of 28.8% at an extra cost of €13, while the extra cost for SR±SA+ROMA was €33, being the gain in terms of NRI superimposable with SR±SA+CA125. CONCLUSIONS: In our study sample SR±SA seems to be the best strategy to triage adnexal masses. Among postmenopausal women, SR±SA+CA125 increased the NRI at a reasonable extra cost. Our data does not justify the use of HE4 and ROMA in the initial triage of adnexal masses.